EP1051217B1 - System zur überwachung einer osmotischen wirkstoffabgabevorrichtung - Google Patents

System zur überwachung einer osmotischen wirkstoffabgabevorrichtung Download PDF

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Publication number
EP1051217B1
EP1051217B1 EP98964191A EP98964191A EP1051217B1 EP 1051217 B1 EP1051217 B1 EP 1051217B1 EP 98964191 A EP98964191 A EP 98964191A EP 98964191 A EP98964191 A EP 98964191A EP 1051217 B1 EP1051217 B1 EP 1051217B1
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EP
European Patent Office
Prior art keywords
beneficial agent
osmotic
delivery device
reservoir
piston
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
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EP98964191A
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English (en)
French (fr)
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EP1051217A1 (de
EP1051217B8 (de
Inventor
Rupal Ayer
Scott D. Jordan
Gregory R. Stewart
Stephen A. Berry
James B. Di Eckenhoff
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Alza Corp
Original Assignee
Eckenhoff Bonnie J
Alza Corp
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Publication date
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Priority to EP02078225A priority Critical patent/EP1260244B1/de
Publication of EP1051217A1 publication Critical patent/EP1051217A1/de
Publication of EP1051217B1 publication Critical patent/EP1051217B1/de
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Publication of EP1051217B8 publication Critical patent/EP1051217B8/de
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Expired - Lifetime legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0004—Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M31/00—Devices for introducing or retaining media, e.g. remedies, in cavities of the body
    • A61M31/002—Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/142—Pressure infusion, e.g. using pumps
    • A61M5/14212—Pumping with an aspiration and an expulsion action
    • A61M5/1424—Manually operated pumps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M2250/00—Specially adapted for animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M25/00—Catheters; Hollow probes
    • A61M25/01—Introducing, guiding, advancing, emplacing or holding catheters
    • A61M25/0105—Steering means as part of the catheter or advancing means; Markers for positioning
    • A61M25/0108—Steering means as part of the catheter or advancing means; Markers for positioning using radio-opaque or ultrasound markers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/14—Infusion devices, e.g. infusing by gravity; Blood infusion; Accessories therefor
    • A61M5/168—Means for controlling media flow to the body or for metering media to the body, e.g. drip meters, counters ; Monitoring media flow to the body
    • A61M5/16831—Monitoring, detecting, signalling or eliminating infusion flow anomalies
    • A61M5/1684—Monitoring, detecting, signalling or eliminating infusion flow anomalies by detecting the amount of infusate remaining, e.g. signalling end of infusion

Definitions

  • the invention relates to an osmotic beneficial agent delivery system. More particularly, the invention relates to a noninvasive monitoring system for monitoring the release of a beneficial agent from an implanted osmotic drug delivery system.
  • Osmotic delivery systems for delivering beneficial agents such as pharmaceuticals for the prevention, treatment, and diagnosis of disease are known in the art.
  • One type of delivery system is the osmotic delivery system in which an osmotic pressure gradient is created to draw an aqueous fluid into a beneficial agent containing member causing the beneficial agent to be delivered.
  • Osmotic delivery systems generally include an implantable member forming a chamber containing the beneficial agent and an osmotic agent which draws an aqueous fluid through the walls of the implantable member causing swelling of the osmotic agent and delivery of the beneficial agent.
  • Some osmotic delivery systems include a single compartment implantable member and contain both the beneficial agent and the osmotic agent within this single compartment. These devices release the beneficial agent by allowing fluid to be imbibed through the wall of the implantable member into the compartment at a rate determined by the permeability of the wall and the osmotic pressure gradient across the wall. The fluid imbibed into the device mixes with the beneficial agent to form an aqueous solution which is dispensed through an exit passageway of the device. Although these devices are effective for delivery of a beneficial agent which is stable and soluble in aqueous and biological fluids, the devices are ineffective for delivery of many types of beneficial agents which are not soluble or stable in aqueous fluids. Examples of osmotic delivery systems of this type include those described in U.S. Patent Nos. 3,845,770 and 3,916,899.
  • the various osmotic delivery systems are designed to deliver a beneficial agent at a controlled rate which will vary depending on many factors including the osmotic material used, the permeability of the walls, and the physical configuration of the delivery device.
  • osmotic delivery devices generally operate very reliably to dispense the desired amount of beneficial agent at the desired rate, it would be beneficial to be able to monitor the delivery of beneficial agent. For example, it would be desirable to be able to detect when the beneficial agent within the delivery device has been completely dispensed and a new device may be needed.
  • Some methods which have been contemplated for monitoring drug delivery from osmotic delivery systems include the measurement of residual amounts of delivered drug in the patient, or radiolabeling the drug composition for detection by X-ray. However, these monitoring methods involve a time delay.
  • Drug delivery rates are generally determined for a particular implantable osmotic device by testing the unimplanted drug delivery device and collection and measuring the delivered drug in a collection vessel. However, these tests will not account for varying conditions which the drug delivery device will encounter when it is actually implanted within the patient. Therefore, monitoring of the operation of the implanted osmotic drug delivery device would be desireable.
  • DE-A-36 10 825 discloses a device for supplying a drug to the bloodstream during a suddenly occurring disease, such as a heart attack, which supplies the drug in one or two rate steps, and wherein the drug can be delivered by manual manipulation through the skin.
  • the means for noninvasively measuring the release of the beneficial agent from the reservoir includes a first radiopaque marker on a portion of the reservoir and a second radiopaque marker on a movable piston positioned within the reservoir and separating the beneficial agent from the osmotic engine.
  • the means for noninvasively measuring the release of the beneficial agent from the reservoir includes a magnetic piston positioned within the implantable reservoir between the osmotic engine and the beneficial agent.
  • a gauge is provided for determining the position of the magnetic piston from an exterior of the animal.
  • the means for noninvasively measuring the release of the beneficial agent from the reservoir includes a marker incorporated in the beneficial agent.
  • the marker provides a detectable response which can be measured noninvasively in body fluids or by-products to monitor release of the beneficial agent within the animal.
  • a method of monitoring performance of an osmotic drug delivery system includes implanting an osmotic drug delivery device having a movable piston in an animal and determining a position of the implanted movable piston within the osmotic drug delivery device from an exterior of the animal.
  • the present invention provides the advantage of noninvasive, real time monitoring of the performance of an implanted osmotic drug delivery system.
  • the present invention relates to performance monitoring of implantable osmotic delivery systems for delivery of beneficial agents to animals and/or humans.
  • Performance monitoring according to the present invention can be achieved by either 1) monitoring the physical configuration of the implanted osmotic delivery device from the exterior of the body to determine the amount of beneficial agent delivered and/or the delivery rate of the beneficial agent; or 2) by use of a performance marker within the beneficial agent to produce a specifically detectable response which can be measured noninvasively in body fluids or by-products.
  • an implantable osmotic delivery system 10 includes an elongated, generally cylindrical housing 12 formed of a first wall 14a and a second wall 14b, an internal movable piston 16, and an exit passage 18 for beneficial agent delivery from the delivery device to the patient.
  • the first and second walls 14a, 14b of the delivery system 10 interengage to define an internal compartment which is divided by the piston 16 into an osmotic chamber 20 and a beneficial agent chamber 22.
  • the second wall 14b of the delivery system includes at least a portion of the wall which is permeable to the passage of aqueous fluid through the wall into the osmotic chamber 20 while the entire wall 14b is impermeable to the osmotic material contained within the osmotic chamber.
  • the fluid permeable portion of the second wall 14b allows fluid to pass into the osmotic agent contained within the chamber 20 and expand the osmotic agent or driving means.
  • the expansion of this osmotic agent also called an osmotic engine, causes the movable piston 16 to slide within the housing dispensing the beneficial agent from the beneficial agent chamber 22 through the exit passage 18.
  • the first wall 14a is preferably impermeable to both external and internal fluids.
  • the first and second walls 14a, 14b of the housing provide an easy method of manufacturing the delivery system 10 by inserting or telescoping the second wall 14b into the first wall 14a to form a liquid and gas impermeable seal between the first and second walls.
  • the two part housing is used for purposes of ease of manufacturing, a one part housing or other housing configurations may also be used.
  • other housing shapes may also be used within the scope of the present invention with the diameter of the delivery system 10 varying depending on the desired delivery rates.
  • the piston 16 is formed of a material which is impermeable to the agents in the two chambers 20, 22.
  • the piston 16 includes a radiopaque dye formulated into the material of the piston such that the piston is visible in an X-ray.
  • a snap-in flow modulator 24 is provided at an end of the first wall 14a and includes the exit passage 18.
  • the flow modulator 24 is also formulated with a radiopaque dye incorporated into the material of the snap-in member.
  • acceptable radiopaque dyes include salts of heavy metals, such as bismuth and titanium, barium salts, and other contrast agents, such as the type used for visualization of small catheters.
  • the design of the implant of FIG. 1 with the radiopaque piston 16 and flow modulator 24 allows the precise location of the piston to be determined with respect to a fixed reference point provided by the flow modulator.
  • the movement of the piston 16 within the housing 12 of the osmotic delivery device of FIG. 1 can be observed noninvasively by performing successive X-rays over time.
  • the information about the position of the piston 16 in real time and the diameter of the osmotic delivery device are used to determine the in vivo release rate for a known diameter drug delivery system 10.
  • the release rate can be determined by either a comparison of two successive X-rays or by comparison of a single X-ray to a known initial state of the osmotic delivery device.
  • FIG. 2 illustrates an alternative embodiment of the invention in which a first radiopaque ring 30 is provided on the dispensing end of the housing wall 14a and a second radiopaque ring 32 is provided on the piston 16.
  • the relative positions of the two radiopaque rings 30, 32 are measured in real time in a series of X-rays or fluoroscope pictures to determine the beneficial agent delivery rate from the delivery system.
  • the second radiopaque ring 32 may be positioned at any location along the piston 16 and may be formed in any shape.
  • the first radiopaque ring 30 may be positioned at any location along the housing 12, as it is the relative locations of these two radiopaque markers 30, 32 which is measured over time.
  • fluoroscopy can also be used to determine the piston position.
  • the walls 14a, 14b of the delivery system should be formed of titanium with a purity of at least about 85%. In this instance, no radiopaque markers are needed to determine piston position by fluoroscopy because the purity of the titanium allows fluoroscopy viewing of the piston position within the walls of the implant.
  • FIG. 3 illustrates another alternative embodiment of the invention in which one or more chemical markers designed to produce a specifically detectable response are incorporated into the beneficial agent to be delivered from an osmotic delivery system.
  • the drug delivery system 40 shown in FIG. 3 includes housing having a single interior chamber 42 containing a beneficial agent which is osmotically active or includes an osmotic agent incorporated into the beneficial agent.
  • the drug delivery system housing includes at least one fluid permeable wall 44 which allows fluid to pass into the chamber 42 but does not allow the beneficial agent and osmotic agent to pass out through the wall.
  • the system 40 also includes a drug delivery or exit passage 46 through which the beneficial agent is delivered to the patient.
  • the chemical markers which can be incorporated within the beneficial agent in the chamber 42 of an osmotic delivery system such as that shown in FIG. 3 include but are not limited to 1) markers that can be detected noninvasively in body tissues or patient fluid samples; 2) peptides and/or proteins that give specific reagent responses; 3) volatile compounds that are vaporized and detected in expelled breath; and 4) metabolites of the drug being delivered that produce measurable responses.
  • markers that can be detected noninvasively in body tissues or patient fluid samples include but are not limited to 1) markers that can be detected noninvasively in body tissues or patient fluid samples; 2) peptides and/or proteins that give specific reagent responses; 3) volatile compounds that are vaporized and detected in expelled breath; and 4) metabolites of the drug being delivered that produce measurable responses.
  • Each of these types of markers allows noninvasive monitoring of the drug delivery by the implanted osmotic delivery device 40.
  • the different types of chemical markers may be used either alone or in combination.
  • the chemical markers according to the present invention can be used in a wide variety of osmotic delivery systems including a system 40 in which the osmotic agent is incorporated in the beneficial agent, as illustrated in FIG. 3, as well as in a delivery system 10 such as is shown in FIGS. 1 and 2 in which the osmotic agent and beneficial agent are maintained in separable compartments by a piston 16 or flexible membrane.
  • the chemical markers may also be used in combination with each other or with other monitoring systems such as the X-ray monitory system described above.
  • Markers that can be detected non-invasively in body tissues or patient fluid samples include azo dyes that can be detected either visually or by diagnostic reaction from patient fluid samples.
  • One such dye is a fluorescent dye, such as fluorescein tagged dextrans, which can be tracked through the body under an external fluorescent light source and/or detected in urine by fluorescent light.
  • Other markers may also be released to the circulatory system and can be measured in skin, tongue, eyes, or other tissues by the use of an external light source.
  • Markers which are detectable in a patient's breath include DMSO (dimethylsulfoxide) which emits an odor detectable with a sulfur detector.
  • FIG. 4 illustrates a further embodiment of the present invention in which an external gauge 50 is used to determine the location of the piston 16 within an osmotic delivery system 10 of the type described above with respect to the embodiment of FIG. 1.
  • the delivery system 10 for use with this embodiment incorporates a magnetic piston 16 which identifies the location of the piston to the external gauge 50.
  • the piston 16 may have magnetic particles imbedded within the piston material, magnetic particles imbedded or sprayed on in a coating of the piston, or the piston may be entirely magnetic.
  • the gauge 50 is a transparent tube-like device containing magnetic particles 52.
  • the gauge 50 has a length which is substantially the same as the length of the implanted delivery system 10. The location of the implanted device 10 can be seen and felt somewhat through the skin of the animal or human in which it is implanted. Thus, when the implanted system 10 is positioned under a layer of skin 70 of the patient, the gauge 50 can be aligned with the implanted system and the magnetic particles 52 within the gauge will be attracted to and congregate at the location of the piston 16 within the delivery device 10 as shown in FIG. 4. Accordingly, a periodic recording of the location of the congregation of the magnetic particles 52 within the gauge 50 provides feedback on system performance so that the amount of beneficial agent that has been released and/or the delivery rate can be determined. Barring significant failures of the piston, piston movement is in direct correlation to beneficial agent delivery rate.
  • FIG. 5 An alternative embodiment of a gauge 80 for determining the location of a piston 16 within an osmotic delivery device 10 is illustrated in FIG. 5.
  • the piston 16 is provided with an internal magnet 82 imbedded in the piston.
  • the magnetic material may also be incorporated into the piston in other ways, as discussed above with respect to the embodiment of FIG. 4.
  • the gauge 80 is a transparent tube having a cylindrical sliding magnet 84 positioned inside the tube.
  • the tube 80 includes markings 86 and the magnet 84 includes an indicator line 88 to facilitate reading of the gauge measurement.
  • the gauge 80 is used in a manner similar to the gauge 50 by periodically placing the clear tube against the implanted delivery device 10 with the ends of the gauge and the delivery device aligned and reading the location of the piston 16 from the markings 86 on the gauge.
  • the accuracy of the monitoring systems of FIGS. 4 and 5 will depend in large part on the accuracy with which the gauges 50, 80 are aligned with the implanted devices 10. Therefore, it would be beneficial to provide protrusions or other types of guides on the implanted device 10 which can be felt through the skin and will help the user to achieve an accurate alignment between the gauges 50, 80 and the implanted device.
  • the implant may be provided with a magnetic band 90 or other indicator at one end corresponding to a magnetic band 92 on the gauge 80.
  • the magnetic bands 90, 92 allow the user to achieve an accurate alignment of the gauge 80 with the implant 10 and prevent unintended inversion of the gauge.
  • the transparent tubes forming the gauges 50, 80 may also be partially opaque with an elongated transparent window for viewing the magnet or magnetic particles.
  • the gauges 50, 80 may also be entirely opaque and have an external indicator or pointer.
  • the gauge 50 employing magnetic particles can also be used with the osmotic delivery system employing the magnet 82 in the piston 16, and alternatively, the gauge 80 may be used with an osmotic delivery device having a piston 16 with magnetic particles incorporated in the lubrication.
  • the performance monitoring system according to the present invention provides more up to date and accurate monitoring over the present practice of measuring residual amounts of beneficial agent in the patient to determine the delivery rate.
  • the expandable driving member or osmotic engine for use in the preferred embodiments of the present invention may be any of the osmotically effective compounds including inorganic and organic compounds that exhibit an osmotic pressure gradient across a semipermeable wall.
  • These osmotically effective compounds as well as manufacturing techniques and materials for formation of the osmotic delivery device itself are described in U.S. Patent No. 5,057,318, which is incorporated herein by reference.
  • the beneficial agents delivered according to the present invention include proteins and proteinaceous compounds having biological activity which may be used to treat disease or other pathological condition. These include, but are not limited to growth hormone, Factor VIII, Factor IX and other coagulation factors, chymotrypsin, trypsinogen, alpha-interferon, beta-galactosidase, lactate dehydrogenase, growth factors, clotting factors, enzymes, immune response stimulators, cytokines, lymphokines, interferons, immunoglobulins, interleukins, peptides, somatostatin, somatotropin analogues, somatomedin-C, Gonadotropic releasing hormone, follicle stimulating hormone, luteinizing hormone, LHRH, LHRH analogues such as leuprolide, nafarelin and goserelin, LHRH agonists and antagonists, growth hormone releasing factor, calcitonin, colchicine, gonadotropins such as
  • agents that may be delivered include ⁇ -antitrypsin, insulin and other peptide hormones, adrenal cortical stimulating hormone, thyroid stimulating hormone, and other pituitary hormones, interferon ⁇ -, ⁇ -, and ⁇ - consensus interferon, erythropoietin, growth factors such as GCSF, GM-CSF, insulin-like growth factor 1, tissue plasminogen activator, CF4, DDAVP, tumor necrosis factor receptor, pancreatic enzymes, lactase, interleukin-1 receptor antagonist, interleukin-2, tumor suppressor proteins, cytotoxic proteins, retroviruses and other viruses, viral proteins, antibodies, recombinant antibodies, antibody fragments and the like.
  • growth factors such as GCSF, GM-CSF, insulin-like growth factor 1, tissue plasminogen activator, CF4, DDAVP, tumor necrosis factor receptor, pancreatic enzymes, lactase, interleukin-1 receptor antagonist, interleukin-2, tumor suppressor proteins,

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Anesthesiology (AREA)
  • Epidemiology (AREA)
  • Vascular Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Magnetic Resonance Imaging Apparatus (AREA)
  • Apparatus For Radiation Diagnosis (AREA)

Claims (10)

  1. Osmotische Abgabevorrichtung (10, 40) zur Abgabe eines wirksamen Mittels an ein Tier, umfassend:
    ein implantierbares Reservoir (22, 42) mit mindestens einer Öffnung (18, 46) zur Abgabe eines im Inneren des Reservoirs enthaltenen wirksamen Mittels an ein Tier;
    einen osmotischen Mechanismus, der die Freisetzung des im Reservoir enthaltenen wirksamen Mittels an ein Tier bewirkt; dadurch gekennzeichnet, dass die osmotische Abgabevorrichtung einen beweglichen Kolben umfasst, und
    eine Vorrichtung zur nicht-invasiven Messung der Freisetzung des wirksamen Mittels aus dem Reservoir von der Aussenseite des Gewebes, in das die Abgabevorrichtung implantiert wurde, entweder durch (1) Überwachung der Kolbenposition der implantierten osmötischen Abgabevorrichtung von der Außenseite des Körpers, um die abgegebene Menge an wirksamem Mittel und/oder die Abgaberate des wirksamen Mittels zu bestimmen; oder durch (2) Verwendung eines Leistungsmarkers im wirksamen Mittel, um eine spezifisch nachweisbare Reaktion zu bewirken, die nicht-invasiv in Körperflüssigkeiten oder Nebenprodukten gernessen werden kann.
  2. Osmotische Abgabevorrichtung (10) nach Anspruch 1, worin die Vorrichtung zur nicht-invasiven Messung der Freisetzung des wirksamen Mittels aus dem Reservoir einen ersten strahlendichten Marker an einem Abschnitt des Reservoirs (24) und einen zweiten Strahlungsdichten Marker am beweglichen Kolben (16), der im Reservoir angeordnet ist und das wirksame Mittel vom osmotischen Mechanismus trennt, umfasst.
  3. Osmotische Abgabevorrichtung nach Anspruch 2, worin das implantierbare Reservoir mindestens einen Durchgang umfasst, der es ermöglicht, dass Flüssigkeit in den osmotischen Mechanismus eindringt und bewirkt, dass der osmotische Mechanismus quillt und den beweglichen Kolben im Reservoir bewegt.
  4. Osmotische Abgabevorrichtung nach Anspruch 1, worin der Kolben magnetisch ist, und worin die Vorrichtung zur nicht-invasiven Messung der Freisetzung des wirksamen Mittels aus dem Reservoir den magnetischen Kolben (16), der im implantierbaren Reservoir zwischen dem osmotischen Mechanismus und dem wirksamen Mittel angeordnet ist, und ein Meßinstrument (50, 80) zur Bestimmung der Position des magnetischen Kolbens von der Außenseite des Tieres aus umfasst.
  5. Osmotische Abgabevorrichtung nach Anspruch 4, worin das Meßinstrument (80) zur Bestimmung der Position des magnetischen Kolbens ein herausnehmbares magnetisches Element (84) umfasst.
  6. Osmotische Abgabevorrichtung nach Anspruch 4 oder Anspruch 5, worin das implantierbare Reservoir eine Vorrichtung (90, 92) zum Abgleichen des Meßinstruments mit dem Reservoir umfasst.
  7. Osmotische Abgabevorrichtung nach einem der Ansprüche 4 bis 6, worin der magnetische Kolben magnetische Teilchen in einem Kolbenschiniermittel umfasst.
  8. Osmotische Abgabevorrichtung (40) nach Anspruch 1, worin die Vorrichtung zur nicht-invasiven Messung der Freisetzung des wirksamen Mittels aus dem Reservoir (42) einen Marker umfasst, der im wirksamen Mittel enthalten ist, wobei der Marker eine nachweisbare Reaktion zur Verfügung stellt, welche nicht-invasiv in Körperflüssigkeiten oder Nebenprodukten gemessen werden kann, um die Freisetzung des wirksamen Mittels zu überwachen.
  9. Osmotische Abgabevorrichtung nach Anspruch 8, worin der Marker ausgewählt ist aus einem Peptid oder Protein, welches spezifische Reagenz-Reaktionen liefert;
       einer Verbindung, die verdampft und in der ausgeatmeten Atemluft nachweisbar ist;
       einem Metaboliten des wirksamen Mittels, wobei der Metabolit meßbare Reaktionen erzeugt;
       und einem Azofarbstoff, der in Flüssigkeitsproben des Patienten nachgewiesen werden kann;
       oder durch Verwendung einer äußeren Lichtquelle in Gewebe meßbar ist.
  10. Osmotische Abgabevorrichtung nach Anspruch 9, worin in dem Fall, in dem der Marker ein Azofarbstoff ist, dieser entweder visuell in Flüssigkeitsproben nachgewiesen wird oder durch eine diagnostische Reaktion in den Flüssigkeitsproben nachweisbar ist.
EP98964191A 1997-12-31 1998-12-21 System zur überwachung einer osmotischen wirkstoffabgabevorrichtung Expired - Lifetime EP1051217B8 (de)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP02078225A EP1260244B1 (de) 1997-12-31 1998-12-21 Verfahren zur Überwachung einer osmotischen Wirkstoffabgabevorrichtung

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US7017897P 1997-12-31 1997-12-31
US70178P 1997-12-31
PCT/US1998/027208 WO1999033513A1 (en) 1997-12-31 1998-12-21 Osmotic drug delivery monitoring system and method

Related Child Applications (1)

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EP02078225A Division EP1260244B1 (de) 1997-12-31 1998-12-21 Verfahren zur Überwachung einer osmotischen Wirkstoffabgabevorrichtung

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EP1051217A1 EP1051217A1 (de) 2000-11-15
EP1051217B1 true EP1051217B1 (de) 2003-08-27
EP1051217B8 EP1051217B8 (de) 2004-07-21

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US (1) US6283953B1 (de)
EP (1) EP1051217B8 (de)
AR (1) AR014231A1 (de)
AT (2) ATE248002T1 (de)
AU (1) AU1937099A (de)
CA (1) CA2316887C (de)
DE (2) DE69817621T2 (de)
DK (1) DK1051217T3 (de)
ES (1) ES2205595T3 (de)
HK (1) HK1032363A1 (de)
PT (1) PT1051217E (de)
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EP1051217A1 (de) 2000-11-15
WO1999033513A1 (en) 1999-07-08
AU1937099A (en) 1999-07-19
CA2316887A1 (en) 1999-07-08
TW381974B (en) 2000-02-11
US6283953B1 (en) 2001-09-04
ATE248002T1 (de) 2003-09-15
PT1051217E (pt) 2003-12-31
DE69834213T2 (de) 2007-01-25
ZA9811879B (en) 1999-09-02
EP1051217B8 (de) 2004-07-21
ATE322928T1 (de) 2006-04-15
DE69817621T2 (de) 2004-03-25
DE69834213D1 (de) 2006-05-24
DK1051217T3 (da) 2003-12-08
CA2316887C (en) 2008-04-08
ES2205595T3 (es) 2004-05-01
DE69817621D1 (de) 2003-10-02
HK1032363A1 (en) 2001-07-20

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